PICALM Regulating the Generation of Amyloid β‐Peptide to Promote Anthracycline‐Induced Cardiotoxicity DOI Creative Commons
Mengni Bao, Xiumeng Hua, X. Chen

и другие.

Advanced Science, Год журнала: 2024, Номер 11(32)

Опубликована: Июнь 27, 2024

Abstract Anthracyclines are chemotherapeutic drugs used to treat solid and hematologic malignancies. However, life‐threatening cardiotoxicity, with cardiac dilation heart failure, is a drawback. A combination of in vivo for single cell/nucleus RNA sequencing vitro approaches elucidate the underlying mechanism. Genetic depletion pharmacological blocking peptides on phosphatidylinositol binding clathrin assembly (PICALM) evaluate role PICALM doxorubicin‐induced cardiotoxicity vivo. Human tissue samples verification. Patients end‐stage failure chemotherapy‐induced have thinner cell membranes compared healthy controls do. Using mice model, it possible replicate corresponding phenotype patients. Cellular changes mice, especially cardiomyocytes, identified using sequencing. Picalm expression upregulated only cardiomyocytes cardiotoxicity. Amyloid β‐peptide production also increased after doxorubicin treatment, which leads greater increase membrane permeability cardiomyocytes. reduce generation amyloid β‐peptide. This alleviates In human patients , elevated as well.

Язык: Английский

Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies DOI Creative Commons
Jifa Zhang, Yinglu Zhang, Jiaxing Wang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Язык: Английский

Процитировано

184

Lipidome disruption in Alzheimer’s disease brain: detection, pathological mechanisms, and therapeutic implications DOI Creative Commons
Sijia He, Ziying Xu, Xianlin Han

и другие.

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 27, 2025

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to involvement of lipid dysregulation in development AD. Nevertheless, precise lipidomic landscape and mechanistic roles lipids pathology remain poorly understood. This review aims highlight significance lipidomics lipid-targeting approaches diagnosis We summarized connection between human brain AD at both genetic species levels. briefly introduced technologies discussed potential challenges areas future advancements field for research. To elucidate central role converging multiple pathological aspects AD, we reviewed current knowledge on interplay major features, including amyloid beta, tau, neuroinflammation. Finally, assessed progresses obstacles lipid-based therapeutics proposed strategies leveraging

Язык: Английский

Процитировано

4

Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's Disease DOI Creative Commons
John H. Viles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(25)

Опубликована: Март 6, 2023

The accumulation of the amyloid-β peptides (Aβ) is central to development Alzheimer's disease. mechanism by which Aβ triggers a cascade events that leads dementia topic intense investigation. self-associates into series complex assemblies with different structural and biophysical properties. It interaction these oligomeric, protofibril fibrillar lipid membranes, or membrane receptors, results in permeability loss cellular homeostasis, key event disease pathology. can have an array impacts on reports included: carpeting effect; detergent ion-channel pore formation. Recent advances imaging interactions are providing clearer picture induced disruption. Understanding relationship between structures will inform therapeutics targeting cytotoxicity.

Язык: Английский

Процитировано

41

Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease DOI
George A. Pantelopulos, Conor B. Abraham, John E. Straub

и другие.

Annual Review of Biophysics, Год журнала: 2024, Номер 53(1), С. 455 - 486

Опубликована: Фев. 21, 2024

Cholesterol has been conjectured to be a modulator of the amyloid cascade, mechanism that produces amyloid-β (Aβ) peptides implicated in onset Alzheimer's disease. We propose cholesterol impacts genesis Aβ not through direct interaction with proteins bilayer, but indirectly by inducing liquid-ordered phase and accompanying liquid-liquid separations, which partition cascade different lipid domains ultimately endocytotic pathways. explore full process context phases induced cholesterol, including protein partitioning into domains, mechanisms endocytosis experienced secretases, pH-controlled activation precursor secretases specific environments. Outstanding questions on essential role are identified for future studies.

Язык: Английский

Процитировано

11

Mechanosensitive Piezo1 channel in physiology and pathophysiology of the central nervous system DOI Creative Commons
Boyi Zong,

Fengzhi Yu,

Xiaoyou Zhang

и другие.

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 102026 - 102026

Опубликована: Июль 31, 2023

Since the discovery of mechanosensitive Piezo1 channel in 2010, there has been a significant amount research conducted to explore its regulatory role physiology and pathology various organ systems. Recently, growing body compelling evidence emerged linking activity health disease central nervous system. However, exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes current on implications for system mechanobiology, retrospects results demonstrating cell types within system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, brain endothelial cells. Furthermore, discusses understanding involvement disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, glioma.

Язык: Английский

Процитировано

21

Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID DOI Open Access
Douglas B. Kell, Asad Khan,

Binita Kane

и другие.

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(2), С. 170 - 170

Опубликована: Янв. 31, 2024

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of variety chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block flow blood microcapillaries and thus cause tissue hypoxia, not simply correlated but in fact, by preceding it, may be chief intermediary POTS, which body's exaggerated 'physiological' response hypoxia. Similar reasoning accounts for symptoms bundled under term 'fatigue'. Amyloids known membrane disruptors, when targets nerve membranes, this can explain neurotoxicity hence autonomic nervous system dysfunction contributes POTS. Taken together view, we indicate microclots serve link POTS fatigue COVID manner at once both mechanistic explanatory. This has clear implications treatment such diseases.

Язык: Английский

Процитировано

9

The structure of tyrosine-10 favors ionic conductance of Alzheimer’s disease-associated full-length amyloid-β channels DOI Creative Commons
Abhijith G. Karkisaval,

Rowan Hassan,

Andrew Nguyen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 13, 2024

Abstract Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer’s disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy characterize channel activities four most prevalent peptides, 1-42 , 1-40 their pyroglutamylated forms (AβpE 3-42 AβpE 3-40 ) correlate them with the peptides’ structural features. Solvent-induced splitting tyrosine-10 is discovered used assess sequestration from solvent membrane insertion. effectively embeds lipid membranes, contains large fraction β-sheet a β-barrel-like structure, multi-subunit pores displays well-defined In contrast, other peptides partially solvent-exposed, contain minimal form less-ordered assemblies, produce irregular currents. These findings illuminate basis through permeabilization may help develop therapies that target Aβ-membrane interactions.

Язык: Английский

Процитировано

8

Exploring pathological link between antimicrobial and amyloid peptides DOI Creative Commons
Yijing Tang, Yanxian Zhang, Dong Zhang

и другие.

Chemical Society Reviews, Год журнала: 2024, Номер 53(17), С. 8713 - 8763

Опубликована: Янв. 1, 2024

Amyloid peptides (AMYs) and antimicrobial (AMPs) are considered as the two distinct families of peptides, characterized by their unique sequences, structures, biological functions, specific pathological targets. However, accumulating evidence has revealed intriguing connections between these peptide in context microbial infection neurodegenerative diseases. Some AMYs AMPs share certain structural functional characteristics, including ability to self-assemble, presence β-sheet-rich membrane-disrupting mechanisms. These shared features enable possess activity acquire amyloidogenic properties. Despite limited studies on AMYs-AMPs systems, cross-seeding phenomenon emerged a crucial factor bidirectional communication pathogenesis diseases host defense against infections. In this review, we examine recent developments potential interplay AMPs, well implications for both infectious By discussing current progress challenges emerging field, account aims inspire further research investments enhance our understanding intricate molecular crosstalk AMPs. This knowledge holds great promise development innovative therapies combat infections disorders.

Язык: Английский

Процитировано

8

Lateral nanoarchitectonics from nano to life: Ongoing challenge in interfacial chemical science DOI Creative Commons
Jingwen Song, Anna Jančík Procházková, Kohsaku Kawakami

и другие.

Chemical Science, Год журнала: 2024, Номер 15(45), С. 18715 - 18750

Опубликована: Янв. 1, 2024

The construction of functional structures within a single plane still has lot challenges. This review article will help us find new groundbreaking directions in lateral nanoarchitectonics toward advanced material organization.

Язык: Английский

Процитировано

7

Spike Protein Fragments Promote Alzheimer’s Amyloidogenesis DOI

Sujian Cao,

Zhiyuan Song,

Jinyu Rong

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2023, Номер 15(34), С. 40317 - 40329

Опубликована: Авг. 16, 2023

Alzheimer's disease (AD) is a major cause of dementia inducing memory loss, cognitive decline, and mortality among the aging population. While amyloid aggregation peptide Aβ has long been implicated in neurodegeneration AD, primarily through production toxic polymorphic aggregates reactive oxygen species, viral infection less explicit role etiology brain disease. On other hand, while COVID-19 pandemic known to harm human organs function, its adverse effects on AD pathobiology conditions remain unclear. Here we first identified amyloidogenic potential

Язык: Английский

Процитировано

16